Budget Impact Analysis of Intensification with iGlarLixi Compared to Alternative Treatment Strategies Among Patients with Type 2 Diabetes Mellitus.

INTRODUCTION: The clinical benefits of treating patients with type 2 diabetes mellitus (T2DM) with fixed-ratio combination of insulin iGlar (iGlar) plus lixisenatide (iGlarLixi) were demonstrated in clinical trials and real-world evidence studies; however, its cost impact to healthcare payers is unknown. METHODS: A budget impact model was developed from a United States (US) payer's perspective for a hypothetical healthcare plan of 1 million people over a 1-year time horizon. In scenario analysis, patients with uncontrolled glycated hemoglobin (HbA1c) treated with 60 units or less of daily insulin (insulin cohort) or oral antidiabetic drugs (OADs) only (OAD cohort) were intensified to iGlarLixi/rapid-acting insulin (RAI)/glucagon-like peptide 1 receptor agonists (GLP-1RA) or iGlarLixi/iGlar/GLP-1RA, respectively. Model inputs from real-world data (RWD) included baseline market shares, proportion of patients intensifying to respective treatments, and dosing inputs; unit costs were obtained from published literature. One-way sensitivity analyses assessed the impact of individual parameters. RESULTS: Intensification with iGlarLixi resulted in the lowest incremental per member per month (PMPM) budget impact compared to other intensifying drugs (iGlar, RAI, and GLP-1RA). In the insulin cohort, the incremental PMPM cost for intensification with iGlarLixi ($0.03) was the lowest among intensifying drugs; GLP-1RA ($72.20) and RAI ($4.81). Similarly, the incremental PMPM cost for intensification with iGlarLixi was the lowest ($1.25) in the OAD cohort among intensifying drugs; GLP-1RA ($321.65) and iGlar ($114.82). In scenario analyses, when equal market intensification shares for iGlarLixi and GLP-1RA were explored, the incremental PMPM cost for iGlarLixi ($0.03) remained lower than GLP-1RA ($2.28) and RAI ($10.44) in the insulin cohort. CONCLUSIONS: Intensification with iGlarLixi was associated with lower costs compared to other treatment intensifications, as well as overall budget reductions compared to pre-intensification when considering cost savings attributable to reduction in HbA1c; therefore, its inclusion for the treatment of T2DM would represent a budget saving.

Clinical Benefits of Treating Patients with Type 2 Diabetes Mellitus with iGlarLixi: A Patient-Level Simulation Study.

INTRODUCTION: The fixed-ratio combination of insulin glargine (iGlar) plus lixisenatide (iGlarLixi) has proven efficacious in clinical trials; however, there is limited evidence of its benefits in a variety of real-world patients with type 2 diabetes mellitus (T2DM) who present in routine clinical practice. METHODS: A large integrated claims and EHR database was used to identify two real-world (RW) cohorts (ages ≥ 18) with T2DM who were eligible for treatment with iGlarLixi. At baseline, the first cohort (insulin cohort) received insulin with or without oral antidiabetic drugs (OADs), and the second cohort (OAD-only cohort) received OADs only. A Monte Carlo patient-level simulation was applied to each cohort based on treatment strategies and efficacies from the LixiLan-L and LixiLan-O trials to estimate reductions in glycated hemoglobin A1C (A1C) and the percentage achieving age-based A1C goals (≤ 7% for ages < 65 and ≤ 8% for ages ≥ 65) at 30 weeks. RESULTS: The RW insulin (N = 3797) and OAD-only (N = 17,633) cohorts differed considerably in demographics, age, clinical characteristics, baseline A1C levels, and background OAD therapies compared to the populations in the Lixilan-L and Lixilan-O trials. Regardless of the cohort description, A1C goals were achieved among 52.6% vs. 31.6% (p < 0.001) of patients in the iGlarLixi vs. the iGlar arms in the insulin cohort simulation, while A1C goals were achieved among 59.9% vs. 49.3% and 32.8% (p < 0.001) of patients in the OAD-only cohort simulation in the iGlarLixi vs. the iGlar and lixisenatide arms, respectively. CONCLUSIONS: Irrespective of the treatment regimen at baseline (insulin vs. OAD only), this patient-level simulation demonstrated that a greater proportion of patients achieved their A1C goals with iGlarlixi compared to iGlar or lixisenatide alone. These findings suggest that the benefits of iGlarLixi extend to clinically distinct RW populations.

Clinical and economic outcomes associated with use of anti-arrhythmic drugs versus ablation in atrial fibrillation.

Aim: To evaluate the clinical and economic impact of antiarrhythmic drugs (AADs) compared with ablation both as individual treatments and as combination therapy without/with considering the order of treatment among patients with atrial fibrillation (AFib). Materials & methods: A budget impact model over a one-year time horizon was developed to assess the economic impact of AADs (amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, and as a group) versus ablation across three scenarios: direct comparisons of individual treatments, non-temporal combinations, and temporal combinations. The economic analysis was conducted in accordance with CHEERS guidance as per current model objectives. Results are reported as costs per patient per year (PPPY). The impact of individual parameters was evaluated using one-way sensitivity analysis (OWSA). Results: In direct comparisons, ablation had the highest annual medication/procedure cost ($29,432), followed by dofetilide ($7661), dronedarone ($6451), sotalol ($4552), propafenone ($3044), flecainide ($2563), and amiodarone ($2538). Flecainide had the highest costs for long-term clinical outcomes ($22,964), followed by dofetilide ($17,462), sotalol ($15,030), amiodarone ($12,450), dronedarone ($10,424), propafenone ($7678) and ablation ($9948). In the non-temporal scenario, total costs incurred for AADs (group) + ablation ($17,278) were lower compared with ablation alone ($39,380). In the temporal scenario, AADs (group) before ablation resulted in PPPY cost savings of ($22,858) compared with AADs (group) after ablation ($19,958). Key factors in OWSA were ablation costs, the proportion of patients having reablation, and withdrawal due to adverse events. Conclusion: Utilization of AADs as individual treatment or in combination with ablation demonstrated comparable clinical benefits along with costs savings in patients with AFib.

A value-based budget impact model for dronedarone compared with other rhythm control strategies.

Aim: The budgetary consequences of increasing dronedarone utilization for treatment of atrial fibrillation were evaluated from a US payer perspective. Materials & methods: A budget impact model over a 5-year time horizon was developed, including drug-related costs and risks for long-term clinical outcomes (LTCOs). Treatments included antiarrhythmic drugs (AADs; dronedarone, amiodarone, sotalol, propafenone, dofetilide, flecainide), rate control medications, and ablation. Direct comparisons and temporal and non-temporal combination scenarios investigating treatment order were analyzed as costs per patient per month (PPPM). Results: By projected year 5, costs PPPM for dronedarone versus other AADs decreased by $37.69 due to fewer LTCOs, treatment with dronedarone versus ablation or rate control medications + ablation resulted in cost savings ($359.94 and $370.54, respectively), and AADs placed before ablation decreased PPPM costs by $242 compared with ablation before AADs. Conclusion Increased dronedarone utilization demonstrated incremental cost reductions over time.

Identification of Patients with Statin Intolerance in a Managed Care Plan: A Comparison of 2 Claims-Based Algorithms.

BACKGROUND: While statins are safe and efficacious, some patients may experience statin intolerance or treatment-limiting adverse events. Identifying patients with statin intolerance may allow optimal management of cardiovascular event risk through other strategies. Recently, an administrative claims data (ACD) algorithm was developed to identify patients with statin intolerance and validated against electronic medical records. However, how this algorithm compared with perceptions of statin intolerance by integrated delivery networks remains largely unknown. OBJECTIVE: To determine the concurrent validity of an algorithm developed by a regional integrated delivery network multidisciplinary panel (MP) and a published ACD algorithm in identifying patients with statin intolerance. METHODS: The MP consisted of 3 physicians and 2 pharmacists with expertise in cardiology, internal medicine, and formulary management. The MP algorithm used pharmacy and medical claims to identify patients with statin intolerance, classifying them as having statin intolerance if they met any of the following criteria: (a) medical claim for rhabdomyolysis, (b) medical claim for muscle weakness, (c) an outpatient medical claim for creatinine kinase assay, (d) fills for ≥ 2 different statins excluding dose increases, (e) decrease in statin dose, or (f) discontinuation of a statin with a subsequent fill for a nonstatin lipid-lowering therapy. The validated ACD algorithm identified statin intolerance as absolute intolerance with rhabdomyolysis; absolute intolerance without rhabdomyolysis (i.e., other adverse events); or as dose titration intolerance. Adult patients (aged ≥ 18 years) from the integrated delivery network with at least 1 prescription fill for a statin between January 1, 2011, and December 31, 2012 (first fill defined the index date) were identified. Patients with ≥ 1 year pre- and ≥ 2 years post-index continuous enrollment and no statin prescription fills in the pre-index period were included. The MP and ACD algorithms were applied to the population, and concordance was examined using individual (i.e., sensitivity, specificity, positive predictive value [PPV], and negative predictive value [NPV]) and overall performance measures (i.e., accuracy, Cohen's kappa coefficient, balanced accuracy, F-1 score, and phi coefficient). RESULTS: After applying the inclusion criteria, 7,490 patients were evaluated for statin intolerance. The mean (SD) age of the population was 51.1 (8.5) years, and 55.7% were male. The MP and ACD algorithms classified 11.3% and 5.4% of patients as having statin intolerance, respectively. The concordance of the MP algorithm was mixed, with negative classification of statin intolerance measures having high concordance (specificity 0.91, NPV 0.97) and positive classification of statin intolerance measures having poor concordance (sensitivity 0.45, PPV 0.21). Overall performance measures showed mixed agreement between the algorithms. CONCLUSIONS: Both algorithms used a mix of pharmacy and medical claims and may be useful for organizations interested in identifying patients with statin intolerance. By identifying patients with statin intolerance, organizations may consider a variety of options, including using nonstatin lipid-lowering therapies, to manage cardiovascular event risk in these patients. DISCLOSURES: This study was funded by Regeneron Pharmaceuticals and Sanofi US. Boklage is employed by, and owns stock in, Regeneron, and Charland is employed by Sanofi. Bellows has received fees from Avenir for advisory board membership and grants from Myriad Genetics, Biogen, Janssen, and National Institutes of Health. Brixner reports advisory board and consultancy fees and grants from Sanofi. Mitchell reports consultancy fees from Sanofi. Study concept and design were contributed by Bellows, Boklage, Charland, and Brixner. Bellows, Sainski-Nguyen, and Olsen took the lead in data collection, along with Mitchell. Data interpretation was performed by Mitchell, along with the other authors. The manuscript was written by Bellows, Sainski-Nguyen, and Olsen and revised by all the authors.

Prasugrel but not high dose clopidogrel overcomes the lansoprazole neutralizing effect of P2Y12 inhibition: Results of the randomized DOSAPI study.

AIMS: The potential negative metabolic interaction between proton pump inhibitors and clopidogrel is an unsolved issue. We hypothesized that doubling the clopidogrel maintenance dose (150 mg) would be less effective than switching to prasugrel 10 mg maintenance dose (MD) to overcome this negative interaction. METHOD AND RESULTS: In a randomized study with a factorial design, 82 stable coronary artery disease patients treated with 75 mg clopidogrel MD and aspirin were assigned to receive in a double blind fashion lansoprazole (30 mg/day) or placebo and to receive in an open fashion 150 mg clopidogrel MD or 10 mg prasugrel MD. The primary endpoint was the relative change in residual platelet reactivity over the 14-day study period [(RPA14day-RPAbaseline)/RPAbaseline]. The effect of doubling the clopidogrel MD on relative change in RPA was neutralized by lansoprazole (-53.6±48.4% versus +0.8±53.7% without and with lansoprazole, respectively, p = 0.02) whereas 10 mg of prasugrel MD dramatically reduced RPA irrespective of lansoprazole co-administration (-81.8 %±24.8% vs. -72.9%±32.9% without and with lansoprazole, respectively, p = NS). Lansoprazole exposure was the only parameter with a significant interaction with RPA among subgroups. CONCLUSION: The higher platelet inhibitory effect obtained by doubling the clopidogrel MD was totally neutralized by the co-administration of lansoprazole. This drug interaction was not observed with prasugrel 10 mg.

Sigmoidal maximal effect modeling of low-density lipoprotein cholesterol concentration and annual incidence of coronary heart disease events in secondary prevention trials.

STUDY OBJECTIVES: To evaluate the relationship between low-density lipoprotein cholesterol (LDL-C) concentration and the annual incidence of combined coronary heart disease (CHD) events­death or nonfatal myocardial infarction (NFMI)­by using sigmoidal maximal effect (sEmax) modeling of published data in various populations at risk for CHD events, and to use the best performing sEmax model generated to calculate the number needed to treat (NNT) to prevent a single CHD death or NFMI event across a range of LDL-C concentrations. DESIGN: Literature-based modeling analysis. PATIENTS: A total of 95,955 patients from 22 published cardiovascular secondary prevention trials. MEASUREMENTS AND MAIN RESULTS: Four distinct sEmax models were created based on intervention approach and CHD event risk for each trial population. Model outputs included the following: Emax (maximum CHD death/NFMI rate), E0 (minimum CHD death/NFMI rate), and fit parameters. The best-fitting sEmax model was compared with linear, log-linear, and logit models, and it was used for calculation of annualized NNT to prevent one CHD death or NFMI event with statins. The best fitting sEmax model was constructed from nine statin intervention trials in 60,483 clinically stable patients with CHD or CHD risk equivalents (Emax = 4.84%/year [95% confidence interval (CI) 4.11­5.41%/year], E0 = 1.24%/year [95% CI 0.64­1.83%/year]) and was superior to linear, log-linear, and logit models. Reduction of CHD death/NFMI incidence diminished at an LDL-C level near 90 mg/dl and became near static at an LDL-C level of 60­70 mg/dl. Annual NNT for LDL-C reduction from a baseline of 130­100 mg/dl, 90, and 70 mg/dl was 129, 104, and 83, respectively, and from a baseline of 100­70 mg/dl was 232. CONCLUSION: An sEmax model fully characterized the relationship between LDL-C concentration and incidence of CHD death or NFMI in a high-risk population receiving statins, with diminishing event reduction at an LDL-C level less than 90 mg/dl, and limited projected event reduction beyond an LDL-C level of ~60­70 mg/dl. As baseline LDL-C level declines, the NNT sharply increases.

Statin use in asthmatics on inhaled corticosteroids is associated with decreased risk of emergency department visits.

OBJECTIVE: Statins are hypothesized to have beneficial effects in asthma management through their pleiotropic anti-inflammatory effects. Several studies have examined this relationship, but have yielded conflicting results. This study investigates the effect of statin use on asthma-related hospitalizations and/or emergency department (ED) visits, and whether this relationship varies by concomitant inhaled corticosteroid (ICS) in a large cohort of asthma patients. METHODS: Subjects with asthma, a recent history of asthma exacerbation, and who were 18 years or older were selected from the population-based Medco Health Solutions administrative database over a 1 year period. Prescription claims for statins and asthma medications, and asthma-related hospitalizations and/or ED visits were ascertained over a 12 month follow-up period. Subjects were stratified into two groups based on their ICS use. RESULTS: A total of 3747 ICS users and 2905 non-ICS users were included in this study. Statin users represented 21% of ICS users and 11% of non-users. Among ICS users, statin use was significantly associated with decreased odds of asthma-related ED visits (OR = 0.77, 95% CI 0.64-0.94, p = 0.008), but not with asthma-related hospitalizations (OR = 1.09, 95% CI 0.92-1.30, p = 0.31). No significant associations were found among non-ICS users (for asthma-related ED visits: OR = 0.92, 95% CI 0.57-1.49, p = 0.73; asthma-related hospitalizations: OR = 1.10, 95% CI 0.85-1.41, p = 0.48). The statistical interactions between ICS and statin use on asthma-related hospitalizations and/or ED visits were not significant. CONCLUSION: Statin use is associated with fewer ED visits in asthma patients who are using ICS.

Prediction of cardiovascular event risk reduction from lipid changes associated with high potency dyslipidemia therapy.

BACKGROUND: Epidemiological data suggests for every 1% reduction in LDL-C there is a corresponding 1-1.5% reduction in cardiovascular events (CVEs). Additionally, for every 2-3% increase in HDL-C there is a reduction in CVEs by 2-4% that is independent of LDL-C. With numerous treatment options for managing dyslipidemia, it is important to evaluate agents that result in the greatest reduction of CVEs. OBJECTIVE: To compare current high-potency dyslipidemia pharmacotherapy with respect to changes in LDL-C and HDL-C and estimate risk reductions for CVEs. METHODS: This study is an analysis of existing published studies for dyslipidemia products marketed in the US. Literature searches were conducted using Medline, International Pharmaceutical Abstracts, Embase, and CINAH to identify trials for niacin extended-release and lovastatin (NER/L); niacin extended-release and simvastatin (NER/S); rosuvastatin (R); and, ezetimibe/simvastatin (E/S) from database inception to 1 May 2009. Demographics and changes from baseline in LDL-C and HDL-C were abstracted and HDL-C to LDL-C change (%Delta-lipids) was created for each therapy. Using a previously validated model the percent reduction in CVEs was estimated for each treatment strategy. RESULTS: Data for 177 treatment arms (120 unique reports), accounting for drug and dose were abstracted. The range in mean +/- SD %Delta-lipids depending on drug dose was: E/S, 58 +/- 6 to 67 +/- 3; R, 51 +/- 5 to 65 +/- 5; NER/L, 33 +/- 7 to 75 +/- 7; and NER/S, 48 to 77 +/- 4. Risk reductions were greatest for NER/statin combinations, with percent risk reductions greater than 77% for NER/S, 2000 mg/10 mg and 83% NER/S, 2000 mg/40 mg. Ignoring medication strengths, reductions in CVEs ranged from 58% for R, 60% for E/S, 61% for NER/L, and 72% for NER/S. LIMITATIONS: There are several potential limitations associated with this study including: publication bias, English only search, limited published studies with NER in combination with L or S, adherent populations, and aggregation of multiple populations. CONCLUSION: The results of the analysis suggest that greater risk reductions in CVEs occur with combination therapies, especially those including niacin extended-release (NER). Up to an 83% risk reduction was estimated for the highest doses of NER and simvastatin (NER/S).

Achieving optimal lipid values in patients with dyslipidemia is associated with reduced risk of cardiovascular events.

BACKGROUND: Cardiovascular (CV) event risk is significantly lower in patients with combined low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) at desired levels versus those without lower levels. However, this has not been investigated relative to specific patterns of baseline lipid abnormalities. OBJECTIVE: To evaluate the association between desired combined lipid value achievement and risk of CV events in patients with different baseline lipid profiles. METHODS: A retrospective managed care database analysis among treatment-naïve adults with elevated CV event risk, ≥12 months follow-up, and full lipid panel from January 1, 2001 to December 31, 2001 plus ≥1 panel before a CV event or study end. Patients were stratified into three baseline cohorts: isolated high LDL-C (Cohort 1), high LDL-C + low HDL-C or high TG (Cohort 2), and high LDL-C, low HDL-C, and high TG (Cohort 3). CV event risk stratified by combined desired lipid value achievement was assessed in each cohort. RESULTS: Achievement of combined desired lipid values/median days to achievement was 29% in 385 days (Cohort 1), 11% in 413 days (Cohort 2), and 7% in 505 days (Cohort 3). Achievement of combined desired lipid values was associated with an adjusted 25%-46% lower CV event risk in Cohort 1 (hazards ratio, 0.75; 95% confidence interval 0.65-0.87), Cohort 2 (hazards ratio, 0.54; 95% confidence interval 0.43-0.67), and Cohort 3 (hazard ratio, 0.54; 95% confidence interval 0.37-0.78). CONCLUSION: Patients with combined desired lipid values had lower risk of CV events versus those without such values. The risk reduction was greatest among patients with multiple lipid abnormalities, suggesting a potential benefit of interventions targeting low HDL-C and/or high TG in addition to high LDL-C.

Risk of cardiovascular events in patients at optimal values for combined lipid parameters.

BACKGROUND: Current prevention guidelines support efforts to achieve optimal high-density lipoprotein (HDL-C) and triglyceride (TG) values, in addition to low-density lipoprotein (LDL-C) in order to reduce cardiovascular (CV) events. The study objective was to evaluate the risk of CV events in patients attaining versus not attaining combined (LDL-C, HDL-C, and TG) optimal lipid values. METHODS/RESULTS: This retrospective cohort analysis was conducted using a 1.1 million member managed care database. Eligible patients had a full lipid panel between 10/1/99 and 9/30/00, were naive to lipid therapy, and had health plan eligibility 12 months pre- and post-index (baseline) lipid laboratory value. Optimal lipid values (LDL-C, HDL-C, and TG) were established using the National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) guidelines, and patients were placed into one of four groups: none, one, two, or three lipid components non-optimal at baseline. The presence of cardiovascular risk, disease, and events were determined by selected International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9 CM) and Current Procedural Terminology (CPT codes). The definition of a CV event included: diagnosis of ischemic heart disease, peripheral arterial disease, stroke/TIA, or revascularization procedure. Odds ratios (OR) for a CV event associated with attainment of each optimal lipid fraction were determined by multivariate logistic regression. The study cohort included 30,348 patients, with a mean follow-up of 27 +/- 8 months. Mean age was 66 +/- 12 years; 16,549 (54%) were male; and 17,289 (57%) patients had coronary heart disease (CHD) or CHD risk equivalent. There were 5955 CV events that occurred in 4059 (13%) study patients. The presence of a single non-optimal lipid value slightly increased CV event risk [OR: 1.06; 95% CI: 0.95-1.18], whereas two or all three non-optimal lipid values significantly increased the risk of a CV event [OR: 1.22; 95% CI: 1.08-1.37; and 1.45; 95% CI: 1.24-1.68, respectively]. LIMITATIONS: As with all large observational databases there are potential limitations including: patient selection bias (e.g., more interventions in patients with greater illness, lack of mortality data, and frequency of lipid monitoring), unknown confounding variables, and potential coding errors. CONCLUSION: Not attaining optimal combined lipid values, independently and significantly, increased the risk of CV events in this large at-risk population with approximately 68,283 patient years of follow-up. The combination of non-attainment of optimal LDL-C with non-attainment of optimal HDL-C or TG values, or both, increased the adjusted risk of CV events by 22-45%. Thus, therapeutic strategies should focus on assessment and management of multiple lipid abnormalities, and not on single lipid risk factor modification.

Achievement of optimal combined lipid values in a managed care setting: is a new treatment paradigm needed?

BACKGROUND: Published guidelines suggest the management of high-density lipoprotein cholesterol (HDL-C) and triglyceride (TG) values after the low-density lipoprotein cholesterol (LDL-C) goal is achieved. OBJECTIVE: This study evaluated the attainment of optimal combined lipid values (LDL-C, HDL-C, and TGs) and associated therapy over time. METHODS: This retrospective cohort analysis was conducted among managed-care patients who had a baseline lipid panel taken between October 1, 1999, and September 30, 2000; were naive to lipid therapy; and had plan eligibility for at least 12 months before and 12 to 36 months after the baseline lipid values. Patients were categorized as elevated-risk primary prevention (ERP) or as coronary heart disease (CHD) and CHD risk equivalents (CHD-RE). The attainment of optimal combined lipid values was assessed at baseline and quarterly thereafter. Associations between lipid values and the use of lipid-altering therapy were assessed using multivariate logistic regression. RESULTS: A total of 30,348 patients were monitored for a mean (SD) duration of 27 (8) months. Mean (SD) age was 66 (12) years and 55% (16,549/30,348) were men; 43% (13,059/30,348) were categorized as ERP and 57% (17,289/30,348) as CHD-RE. Combined lipid values were optimal in 14% (4167/30,348),18% (5508/30,348), and 22% (2936/13,100) of patients at baseline, 12 months, and 36 months, respectively. After 36 months, 78% (10,164/13,100) of patients did not attain optimal combined lipid values. Lipid therapy, primarily statin monotherapy (87% [7992/ 92251), was prescribed in 30% (9225/30,348) of patients. After 36 months, 34% (4492/13,100) of patients had isolated elevated LDL-C and 20% (2588/13,100) had non-optimal HDL-C and/or TGs. Lipid therapy was associated with the attainment of optimal combined values for LDL-C and TGs (both, P < 0.05), but not for HDL-C. Because the study was retrospective, causality cannot be determined. CONCLUSIONS: Based on the results of this study, use of combination lipid therapy and targeted therapy aimed at the specific lipid abnormalities may increase the attainment of optimal lipid parameters.

Adherence and persistence with single-dosage form extended-release niacin/lovastatin compared with statins alone or in combination with extended-release niacin.

BACKGROUND: Lipid-lowering therapies have been shown to reduce cardiovascular events and mortality; patient cooperation with therapy varies. A fixed-dose combination product, extended-release niacin/lovastatin (ERNL), has been shown to be beneficial in lipid management; however, little is known regarding patient behavior with ERNL therapy. OBJECTIVE: To evaluate patient adherence and persistence with ERNL, statin monotherapy (SM), extended-release niacin (ERN) monotherapy, and ERN plus a statin (ERN-S). METHODS: Prescription claims for lipid-lowering therapies were obtained from a pharmacy benefits manager between 2002 and 2003. Claims for a total of 2389 patients were analyzed for adherence and persistence, using medication possession ratios (MPRs) and proportions of days covered (PDCs). Adherence and persistence were defined, respectively, as an MPR or PDC greater than or equal to 0.80. Logistic regression was conducted to detect differences among groups. Covariates included age, gender, copay, and number of lipid-lowering therapies, a surrogate for disease severity. RESULTS: Average MPR scores were relatively high in all groups at 0.88, 0.81, 0.89, and 0.90 for ERNL, SM, ERN, and ERN-S, respectively. The adjusted odds ratio for adherence was lowest for SM (0.69), which was statistically significant compared with ERN-S (1.43), but not ERNL (1.00) or ERN (0.74). Persistence outcomes were poor in all groups. By the fourth quarter, patients receiving ERN-S (OR 1.31) had significantly greater persistence than those receiving ERN (OR 0.41) and SM (0.61), but not those receiving ERNL (OR 1.00). CONCLUSIONS: Managed care patients tended to be adherent to chronic lipid-lowering therapies, based on a mean MPR greater than 0.8. However, most patients failed to persist for at least 6 months.

Burden of illness of hepatitis C from a managed care organization perspective.

OBJECTIVES: The objectives of this study were to: (1). determine the total hepatitis C virus (HCV)related and total healthcare costs (HCV plus other co-morbidities) of patients with HCV in a managed care organization; (2). determine total healthcare costs of HCV patients with and without a human immunodeficiency virus (HIV) infection as a comorbidity. METHODS: The study design was a retrospective analysis of a medical and pharmacy claims database of patients diagnosed with HCV in a 325000 member managed care organization. Patients diagnosed with HCV and 12 months of continuous eligibility in the managed care organization from January 1997 through December 1999 were included in the study. The main outcome measures of the study were the total healthcare costs and HCV-related healthcare costs and the impact of HIV as a co-morbidity on these costs. RESULTS: The study identified 614 patients meeting the inclusion criteria. The study population was 58% male and had a mean age of 46 (+/- 10.6) years. In patients receiving interferon-alpha, their median total healthcare costs exceeded US dollars 4600 and the median HCV-related costs exceeded US dollars 2470. The total healthcare costs of HCV patients with HIV as a co-morbidity were significantly larger than patients without this comorbidity. CONCLUSION: HCV represents a very important disease to managed care organizations. Patients with this disease require costly drug therapies and consume significant health care resources. Additional research is needed to more fully characterize future clinical and economic outcomes as new agents become available.

The effect of sepsis during parenteral nutrition on hepatic microsomal function in rats.

STUDY OBJECTIVE: To investigate the effect of sepsis during parenteral nutrition on hepatic cytochrome P450 (CYP) activity in rats. DESIGN: Prospective, randomized, controlled study. SETTING: University-based animal research laboratory. ANIMALS: Twenty adult male Sprague-Dawley rats. INTERVENTION: The animals were cannulated intravenously and randomized to receive parenteral nutrition (PN), intravenous live Escherichia coli 4 x 10(8) colony-forming units/100 g body weight for 2 consecutive days with PN (PNEC), or chow (CH). MEASUREMENTS AND MAIN RESULTS: Both PN alone and PNEC resulted in a progressive decline in hepatic CYP concentration compared with CH (0.53 +/- 0.10, 0.41 +/- 0.17, and 0.35 +/- 0.14 nmol/mg microsomal protein, respectively, p < 0.05). Parenteral nutrition alone was associated with a 57% decrease in isoenzyme ethoxycoumarin-O-deethylase activity (ECOD) compared with CH, but sepsis did not further decrease ECOD activity any more than PN alone (0.103 +/- 0.049, 0.044 +/- 0.018, and 0.050 +/- 0.020 nmol/mg microsomal protein/min, respectively, p < 0.05). CONCLUSION: Hepatic CYP concentration declines with PN and is further decreased when compounded by sepsis. The disproportional decrease in ECOD activity relative to CYP concentration with PN is unchanged by sepsis, indicating a selective alteration in hepatic isoenzymes by PN.